ISOLATION AND CHARACTERIZATION OF A NOVEL ZINC-FINGER PROTEIN WITH TRANSCRIPTIONAL REPRESSOR ACTIVITY

To identify genes that can repress the expression of growth regulatory molecules, a human fetal cDNA library was screened with a degenerate oligonucleotide that corresponds to the conserved stretch of 6 amino a cids connecting successive zinc-finger regions in the Wilms' tumor sup pressor/Egr-1 family of DNA-binding proteins. One clone, designated zi nc-finger protein 174 (ZNF174), corresponds to a putative transcriptio n factor with three zinc fingers and a novel finger-associated domain, designated the SCAN box, The three Cys(2)-His(2)-type zinc fingers ar e positioned at the carboxyl terminus, while the 65-amino acid finger- associated SCAN box is located near the amino terminus, Chromosomal lo calization using somatic cell hybrid analysis and fluorescent in. situ hybridization mapped the gene for ZNF174 to human chromosome 16p13.3. The 2.5-kilobase transcript from this gene is expressed in a variety of human organs, but most strongly in adult testis and ovary. Fusion o f the upstream regulatory region of ZNF174 to the DNA-binding domain o f GAL4 revealed that the gene could confer a repression function on th e heterologous DNA-binding domain. ZNF174 selectively repressed report er activity driven by the platelet-derived growth factor-B chain and t ransforming growth factor-beta(1) promoters and bound to DNA in a spec ific manner. This member of the C2H2-type zinc-finger family is a nove l transcriptional repressor.